Unravelling the TL1A-DR3 axis in Hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder that presents with both cutaneous manifestations and extracutaneous comorbidities. Current treatment options include antibiotics and biologics; however, treatment failure is common and often surgical intervention is required for acceptable control. Anti-TL1A therapies have recently gained attention in HS treatment due to their ability to inhibit the TL1A/DR3 axis, a key signaling pathway driving immune cell activity and fibrosis. Participant recruitment for the phase 2b trial (NCT06956235) assessing the efficacy of anti-TL1A therapy tulisokibart in moderate-to severe HS was reported on 1 December, 2025 to be completed. This review aims to explore the potential links between the TL1A and HS by synthesizing immune mechanisms of HS pathogenesis with existing data of the TL1A/DR3 axis in immune pathways. A discussion highlighting the potential for anti-TL1A therapies as a class that simultaneously addresses fibrosis and comorbidities of HS is also presented, and future directions to address knowledge gaps are also proposed.